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髓过氧化物酶与类风湿关节炎中的氧化应激。

Myeloperoxidase and oxidative stress in rheumatoid arthritis.

机构信息

Department of Medicine, University of Otago, Christchurch, Christchurch 8140, New Zealand.

出版信息

Rheumatology (Oxford). 2012 Oct;51(10):1796-803. doi: 10.1093/rheumatology/kes193. Epub 2012 Jul 19.

DOI:10.1093/rheumatology/kes193
PMID:22814531
Abstract

OBJECTIVE

To determine whether MPO contributes to oxidative stress and disease activity in RA and whether it produces hypochlorous acid in SF.

METHODS

Plasma and where possible SF were collected from 77 RA patients while 120 healthy controls supplied plasma only. MPO and protein carbonyls were measured by ELISAs. 3-Chlorotyrosine in proteins and allantoin in plasma were measured by mass spectrometry.

RESULTS

Plasma MPO concentrations were significantly higher in patients with RA compared with healthy controls [10.8 ng/ml, inter-quartile range (IQR): 7.2-14.2; P<0.05], but there was no significant difference in plasma MPO protein concentrations between RA patients with high disease activity (HDA; DAS-28 >3.2) and those with low disease activity (LDA; DAS-28 ≤ 3.2) (HDA 27.9 ng/ml, 20.2-34.1 vs LDA 22.1 ng/ml, 16.9-34.9; P>0.05). There was a significant relationship between plasma MPO and DAS-28 (r=0.35; P=0.005). Plasma protein carbonyls and allantoin were significantly higher in patients with RA compared with the healthy controls. MPO protein was significantly higher in SF compared with plasma (median 624.0 ng/ml, IQR 258.4-2433.0 vs 30.2 ng/ml, IQR 25.1-50.9; P<0.0001). The MPO present in SF was mostly active. 3-Chlorotyrosine, a specific biomarker of hypochlorous acid, was present in proteins from SF and related to the concentration of MPO (r=0.69; P=0.001). Protein carbonyls in SF were associated with MPO protein concentration (r=0.40; P=0.019) and 3-chlorotyrosine (r=0.66; P=0.003).

CONCLUSION

MPO is elevated in patients with RA and promotes oxidative stress through the production of hypochlorous acid.

摘要

目的

确定 MPO 是否会导致 RA 中的氧化应激和疾病活动,并确定其是否在 SF 中产生次氯酸。

方法

收集了 77 例 RA 患者的血浆和尽可能多的 SF,而 120 名健康对照者仅提供了血浆。通过 ELISA 测量 MPO 和蛋白质羰基。通过质谱法测量蛋白质中的 3-氯酪氨酸和血浆中的别嘌呤醇。

结果

与健康对照组相比,RA 患者的血浆 MPO 浓度明显升高[10.8ng/ml,四分位距(IQR):7.2-14.2;P<0.05],但高疾病活动(DAS-28>3.2)与低疾病活动(DAS-28≤3.2)RA 患者之间的血浆 MPO 蛋白浓度无显著差异(HDA 27.9ng/ml,20.2-34.1 与 LDA 22.1ng/ml,16.9-34.9;P>0.05)。血浆 MPO 与 DAS-28 呈显著相关(r=0.35;P=0.005)。与健康对照组相比,RA 患者的血浆蛋白质羰基和别嘌呤醇明显升高。SF 中的 MPO 蛋白明显高于血浆(中位数 624.0ng/ml,IQR 258.4-2433.0 与 30.2ng/ml,IQR 25.1-50.9;P<0.0001)。SF 中存在的 MPO 主要是活跃的。3-氯酪氨酸是次氯酸的特异性生物标志物,存在于 SF 中的蛋白质中,与 MPO 的浓度相关(r=0.69;P=0.001)。SF 中的蛋白质羰基与 MPO 蛋白浓度(r=0.40;P=0.019)和 3-氯酪氨酸(r=0.66;P=0.003)相关。

结论

RA 患者的 MPO 升高,并通过产生次氯酸促进氧化应激。

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